Pharmaceutical active substances are frequently incorporated in a matrix formed from a biodegradable polymer for intracorporeal administration. The polymer matrix therefore represents an active substance depot (slow release) which is inserted/implanted in the body of the patient to be treated by surgery, and there gradually releases the active substance. The polymer matrix then degrades so that no further surgery is required for extraction of the polymer matrix. For example, the active substance charged polymer matrix may be introduced directly into the vascular system of a patient as an active substance depot or may be used to charge a cavity which forms part of the implant and from which the active substance is then released after implantation. Furthermore, the active substance charged polymer matrix may be applied to implants as a coating, e.g., heart pacemakers, defibrillators and stents, to assist in the healing process in the surrounding tissue and counteract tissue irritations caused by the release of active substances. Based on studies of the applicant it has proved particularly advantageous to use polylactides, particularly poly-L-lactides, as biodegradable polymers of the polymer matrix.
WO 2005/004945 discloses a method in which an active substance charged polymeric coating is heated on a stent for a predeterminable time above a glass transition temperature of the polymer in order to reduce the in vivo elution rate of an active substance. The experiments described relate only to the polymer ethylene vinyl alcohol copolymer (EVAL).
An essential criterion for suitability of polymer matrices for the release of active substances is, among other things, high reproducibility of the elution characteristic over time. However, studies of the applicant have shown that on a polylactide matrix the elution characteristic is dependent on the length of the storage time. In other words, the polylactide matrix ages after its manufacture, due mainly to crystallisation processes, and this morphological change influences the elution of the active ingredient. Consequently, measures would be required to stabilise the elution characteristic during the storage period. However, of the active substance from the polylactide matrix should in this case not be reduced but increased further, if possible.